Consumers are increasingly interested in cosmetics that treat, mitigate, or delay the signs of aging or aged skin. During the aging process, the complexion of the skin, i.e., the color and appearance of the skin, deteriorates slowly from aging and/or exposure to sunlight. Dermatological signs of chronologically, hormonally-aged, or photo-aged skin manifest themselves in lines and wrinkles, sagging, dullness, discoloration, uneven tone, and/or rough texture. Further, aged skin lacks strength and elasticity and is therefore fragile. The cosmetics industry is actively pursuing products that may be used to reduce signs of aging or aged skin (anti-aging compounds) and thereby provide anti-wrinkle, rejuvenating, and skin coloring benefits.
Autophagy is a catabolic process that helps in maintaining an unequivocal balance between the synthesis and degradation of proteins, and subsequent recycling of cellular products. Autophagy is a mechanism for recycling and detoxifying cellular components and organelles, i.e., it gets rid of bulky cell components such as damaged organelles (e.g. mitochondria) and protein aggregates. In particular, autophagy makes it possible to regulate, repair and eliminate proteins with a long service life in skin cells (e.g., fibroblasts, melanocytes, and/or keratinocytes), thus ensuring a control during differentiation and aging of human skin.
On the cellular plane, the autophagy mechanism comprises four stages: (1) initiation, (2) formation of an initial vacuole (“autophagosome”), which sequesters the cytoplasmic material, (3) the maturation of the autophagosome into a degradative vacuole, and (4) fusion with the lysosome until the degradation of the sequestered material is achieved. If this process breaks down or slows down, damaged organelles and proteins will accumulate within the cell interfering with normal cellular functions, especially protein synthesis, and ultimately cell viability.
WIPI-1 (Atg-18) is a member of the WD40 repeat proteins, and has a 7-bladed propeller structure that allows reversible protein-protein interactions. WIPI-1 also contains a conserved motif for interaction with phospholipids. These structural features make WIPI-1 a good candidate to be a part of the autophagasome vacuole, and recent studies have confirmed its involvement in autophagy in human cells. Autophagy 7:3, 279-296; March 2011; © 2011 Landes Bioscience and Anne Simonsen and Sharon A. Tooze, “Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes,” J. Cell Biol. Vol. 186 No. 6 773-782. It has been demonstrated that endogenous WIPI-1 protein co-localizes with the autophagosomal marker LC3 at punctate cytoplasmic structures in human cells to initiate the formation of the vacuole. Proikas-Cezanne et al., Human WIPI-1 puncta-formation: A novel assay to assess mammalian autophagy, FEBS Letters 581 (2007) 3396-3404.
U.S. Patent Publication No. 20120225092 entitled Cosmetic Use of Skin Cell Autophagy Activators discusses the use of various compounds to increase autophagy within skin cells through the up-regulation of the ATG5-12 and MAP-LC3 protein complexes. Also, Hu et al., WIPI1 Coordinates Melanogenic Gene Transcription and Melanosome Formation Via TORC1 Inhibition, Journal of Biological Chemistry, vol. 286, No. 14, pp. 12509-12523 (2011), discloses WIPI1's influence upon the regulation of melanosome formation.
Thus, a need remains for cosmetic compositions which reduce the manifestations of skin aging associated with reduced autophagy activity within skin cells. It is therefore an object of the invention to provide new compositions and methods for increasing, maintaining and/or restoring autophagy activity levels within skin cells. It is a further object of the invention to improve the overall appearance of skin, including treating, reversing, and/or preventing signs of skin aging or damage, such as wrinkles, fine lines, discoloration, loss of tone, loss of elasticity, thinning, etc. by up-regulating WIPI-1 within skin cells.
The foregoing discussion is presented solely to provide a better understanding of nature of the problems confronting the art and should not be construed in any way as an admission as to prior art nor should the citation of any reference herein be construed as an admission that such reference constitutes “prior art” to the instant application.